A 24-year-old woman on phenytoin 300 mg/day has a steady-state serum level of 12 micrograms/mL. The neurologist increases the dose to 350 mg/day. At the new steady state her level is measured at 26 micrograms/mL with nystagmus. This disproportionate rise in serum concentration occurs because:

• A Phenytoin induces CYP2C9, accelerating its own clearance
• B The extended-release formulation has dose-dependent bioavailability
• C Phenytoin displaces albumin-bound bilirubin, raising free fraction
• D Hepatic metabolism becomes saturated and shifts from first-order to zero-order kinetics ✓

Explanation

At therapeutic concentrations the CYP-mediated hydroxylation of phenytoin approaches saturation, so clearance falls as concentration rises and small dose increments produce large, unpredictable jumps in plasma levels. This Michaelis-Menten behaviour is why dose changes near the therapeutic range should be made in small steps of 25 to 50 mg. Option A is wrong because phenytoin does not meaningfully autoinduce its own metabolism; autoinduction is the hallmark of carbamazepine.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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Written and medically reviewed by the StethoPrep medical team.